Early Access to Electronic Health Records May Influence the Patient Experience.

In a recent Hot Topics column, Mehmet Sitki Copur, MD, FACP, et al discussed the pros and cons of patients receiving test results early through electronic medical records.

Mode of Detection of Second Events in Routine Surveillance of Early Stage Breast Cancer Patients.

INTRODUCTION: NCCN and ASCO guidelines recommend breast cancer (BC) follow-up to include clinical breast examination (CBE) every 6 months and annual mammography (AM) for 5 years. Given limited data to support CBE, we evaluated the modes of detection (MOD) of BC-events in a contemporary practice. METHODS: We conducted a retrospective review of registry patients with early stage BC (DCIS, Stage I or II) diagnosed between 2010 and 2015 with at least 5 years of follow-up. Second events were defined as malignant (contralateral primary, ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, regional node recurrence or distant relapse) or benign. MOD was categorized as patient complaint, clinical examination or breast imaging. RESULTS: Sixty-three of 351 BC patients experienced second events. 15 had BC malignant events, including 4 distant disease, 5 contralateral primary, and 3 IBTR. 7/8 of IBTR and contralateral primary BC were AM detected. Patient complaints identified 4/4 distant relapses. Clinical exam identified 2/2 chest wall recurrences in post-mastectomy patients. CONCLUSIONS: Only 2.8% (10/351) of early stage BC patients experienced recurrence during 5 years of follow-up. AM was the predominate MOD of both IBTR and new contralateral primary following breast conserving therapy. Patient complaints prompted evaluation for distant disease. Provider CBE was MOD in only 2/351, 0.6% 95% CI (2.1%-0.1%) of patients as chest wall recurrences postmastectomy. Given modern enhancements to imaging and lower recurrence rates, this data encourages the reassessment of guidelines for every 6-month CBE and provides basis to study telehealth in survivorship care.

Complete Pathologic Response to Neoadjuvant Chemoimmunotherapy and Oxaliplatin-Induced Fever Associated With IL-6 Release in a Patient With Locally Advanced Colon Cancer

Neoadjuvant systemic therapy is a preferred treatment approach for a number of tumor types due to many potential advantages over upfront surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. For colon cancer, current standard of care is upfront surgery followed by adjuvant systemic therapy in high-risk patients. Concerns about inaccurate radiological staging and tumor progression during preoperative treatment, as well the lack of randomized data demonstrating benefit, are among the reasons for the limited use of neoadjuvant therapy in this disease. Locally advanced colon cancer, defined as primary colon cancer with direct invasion into the adjacent structures or extensive regional lymph node involvement, is not always amenable to pathological complete resection, and when attempted it comes with high incidence of postoperative morbidity and mortality because of the required multivisceral resection. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been promising with downstaging of disease and higher rates of R0 resection. Here, we report a case of a patient with locally advanced, unresectable, mismatch repair deficient sigmoid colon cancer who was treated with neoadjuvant chemoimmunotherapy followed by surgical resection leading to a complete pathologic response after preoperative systemic chemoimmunotherapy.

Altered Metabolic Profile of Triglyceride-Rich Lipoproteins in Gut-Lymph of Rodent Models of Sepsis and Gut Ischemia-Reperfusion Injury.

BACKGROUND: Triglyceride-rich lipoproteins are important in dietary lipid absorption and subsequent energy distribution in the body. Their importance in the gut-lymph may have been overlooked in sepsis, the most common cause of critical illness, and in gut ischemia-reperfusion injury, a common feature of many critical illnesses. AIMS: We aimed to undertake an exploratory study of triglyceride-rich lipoprotein fractions in gut-lymph using untargeted metabolic profiling to identify altered metabolites in sepsis or gut ischemia-reperfusion. METHODS: The gut-lymph was collected from rodent sham, sepsis, and gut ischemia-reperfusion models. The triglyceride-rich lipoprotein-enriched fractions isolated from the gut-lymph were subjected to a dual metabolomics analysis approach: non-polar metabolite analysis by ultra-high performance liquid chromatography-mass spectrometry and polar metabolite analysis by gas chromatography-mass spectrometry. RESULTS: The metabolite analysis of gut-lymph triglyceride-rich lipoprotein fractions revealed a significant increase (FDR-adjusted P value < 0.05) in myo-inositol in the sepsis group and monoacylglycerols [(18:1) and (18:2)] in gut ischemia-reperfusion. There were no significantly increased specific metabolites in the lipoprotein-enriched fractions of both sepsis and gut ischemia-reperfusion. In contrast, there was a widespread decrease in multiple lipid species in sepsis (35 out of 190; adjusted P < 0.05), but not in the gut ischemia-reperfusion. CONCLUSIONS: Increased levels of myo-inositol and monoacylglycerols, and decreased multiple lipid species in the gut-lymph triglyceride-rich lipoprotein fraction could be candidates for new biomarkers and/or involved in the progression of sepsis and gut ischemia-reperfusion pathobiology.

Accelerated bone growth in vitro by the conjugation of BMP2 peptide with hydroxyapatite on titanium alloy.

Titanium alloys have been widely used in orthopedic practice due to their inherent bioactivity, however it is still insufficient to truly and reliably incorporate into living bone. In this work, polydopamine film was employed to induce the growth of hydroxyapatite (HA) on titanium alloy to enhance its osteoconductivity. Bone morphogenetic protein-2 (BMP2) peptide was absorbed into the HA particles for osteoinductivity. The precipitation of HA and the existence of BMP2 peptide were examined by X-ray diffraction, X-ray photoelectron spectroscopy and fluorescence microscopy. The dissolution of HA and the release of BMP2 peptide were monitored by measuring the concentrations of calcium ions and BMP2 peptide in phosphate buffered saline solution, respectively. The effect of BMP2 peptide incorporated into HA coating on bone growth was evaluated in vitro by cell culture tests, including cell attachment, alkaline phosphatase (ALP) activity, and gene expression. The results show that the HA particles grown on the substrate are mediated by the polydopamine film. The BMP2 peptide is distributed uniformly on HA-coated substrate and released in a sustained manner. Moreover, the conjunction of HA and BMP2 peptide increases cell adhesion, ALP activity and gene expression of osteogenic markers, which are potentially useful in the development of enhanced orthopedic medical devices.

Covalently grafted BMP-7 peptide to reduce macrophage/monocyte activity: an in vitro study on cobalt chromium alloy.

Cobalt chromium (CoCr) alloy is widely used in orthopedic implants but its functional longevity is susceptible to inflammation related complications. Reduction of the development of chronic inflammation on the biomaterial surface would enhance direct bone-implant bonding and improve implant survival and long-term results. The BMP-7 peptide was derived from the knuckle epitope of bone morphogenic protein-7 (BMP-7) and was conjugated via a cysteine amino acid at the N-terminus. Mouse RAW 264.7 monocytes/macrophages were seeded on the CoCr substrates and inflammation was induced via lipopolysaccharide (LPS) challenge. The effects of BMP-7 peptide on inflammation were evaluated by measuring the expression of inflammatory markers like toll-like receptor-4 (TLR-4), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1). ELISA and qPCR assays were used to study the inflammatory signals. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. Utilizing the reactivity of polydopamine films to immobilize BMP-7 peptide onto metal substrates may provide a promising approach for applications in situations where reduction of inflammation around implants would be beneficial in improving surgical outcome, bone healing, and implant integration.

Unitary-quantum-lattice algorithm for two-dimensional quantum turbulence.

Quantum vortex structures and energy cascades are examined for two-dimensional quantum turbulence (2D QT) at zero temperature. A special unitary evolution algorithm, the quantum lattice algorithm, is employed to simulate the Bose-Einstein condensate governed by the Gross-Pitaevskii (GP) equation. A parameter regime is uncovered in which, as in 3D QT, there is a short Poincaré recurrence time. It is demonstrated that such short recurrence times are destroyed by stronger nonlinear interaction. The similar loss of Poincaré recurrence is also seen in the 3D GP equation. Various initial conditions are considered in an attempt to discern if 2D QT exhibits inverse cascades as is seen in 2D classical turbulence (CT). In our simulation parameter regimes, no dual cascade spectra were observed for 2D QT-unlike that seen in 2D CT.

Poincaré recurrence and spectral cascades in three-dimensional quantum turbulence.

The time evolution of the ground state wave function of a zero-temperature Bose-Einstein condensate (BEC) gas is well described by the Hamiltonian Gross-Pitaevskii (GP) equation. Using a set of appropriately interleaved unitary collision-stream operators, a qubit lattice gas algorithm is devised, which on taking moments, recovers the Gross-Pitaevskii (GP) equation under diffusion ordering (time scales as length(2)). Unexpectedly, there is a class of initial states whose Poincaré recurrence time is extremely short and which, as the grid resolution is increased, scales with diffusion ordering (and not as length(3)). The spectral results of J. Yepez et al. [Phys. Rev. Lett. 103, 084501 (2009).] for quantum turbulence are revised and it is found that it is the compressible kinetic energy spectrum that exhibits three distinct spectral regions: a small-k classical-like Kolmogorov k(-5/3), a steep semiclassical cascade region, and a large-k quantum vortex spectrum k(-3). For most evolution times the incompressible kinetic energy spectrum exhibits a somewhat robust quantum vortex spectrum of k(-3) for an extended range in k with a k(-3.4) spectrum for intermediate k. For linear vortices of winding number 1 there is an intermittent loss of the quantum vortex cascade with its signature seen in the time evolution of the kinetic energy E(kin)(t), the loss of the quantum vortex k(-3) spectrum in the incompressible kinetic energy spectrum as well as the minimalization of the vortex core isosurfaces that would totally inhibit any Kelvin wave vortex cascade. In the time intervals around these intermittencies the incompressible kinetic energy also exhibits a multicascade spectrum.

Superfluid turbulence from quantum Kelvin wave to classical Kolmogorov cascades.

The main topological feature of a superfluid is a quantum vortex with an identifiable inner and outer radius. A novel unitary quantum lattice gas algorithm is used to simulate quantum turbulence of a Bose-Einstein condensate superfluid described by the Gross-Pitaevskii equation on grids up to 5760(3). For the first time, an accurate power-law scaling for the quantum Kelvin wave cascade is determined: k(-3). The incompressible kinetic energy spectrum exhibits very distinct power-law spectra in 3 ranges of k space: a classical Kolmogorov k(-(5/3)) spectrum at scales greater than the outer radius of individual quantum vortex cores and a quantum Kelvin wave cascade spectrum k(-3) on scales smaller than the inner radius of the quantum vortex core. The k(-3) quantum Kelvin wave spectrum due to phonon radiation is robust, while the k(-(5/3)) classical Kolmogorov spectrum becomes robust on large grids.

Entropic lattice Boltzmann representations required to recover Navier-Stokes flows.

There are two disparate formulations of the entropic lattice Boltzmann scheme: one of these theories revolves around the analog of the discrete Boltzmann H function of standard extensive statistical mechanics, while the other revolves around the nonextensive Tsallis entropy. It is shown here that it is the nonenforcement of the pressure tensor moment constraints that lead to extremizations of entropy resulting in Tsallis-like forms. However, with the imposition of the pressure tensor moment constraint, as is fundamentally necessary for the recovery of the Navier-Stokes equations, it is proved that the entropy function must be of the discrete Boltzmann form. Three-dimensional simulations are performed which illustrate some of the differences between standard lattice Boltzmann and entropic lattice Boltzmann schemes, as well as the role played by the number of phase-space velocities used in the discretization.